Variations in the NMDA receptor subunit 2B gene ( GRIN2B ) and schizophrenia: A case‐control study

A well established model for the pathophysiology of schizophrenia postulates a role for the NMDA‐mediated glutamate transmission. The human gene coding for the 2B subunit of the NMDA receptor ( GRIN2B ) is considered a candidate based on its selective expression in brain. To evaluate the hypothesis that GRIN2B acts as a major gene in determining susceptibility to schizophrenia, a case‐control association study was performed. Five single nucleotide polymorphisms (SNPs) were genotyped in 188 Italian patients and 156 control subjects. The association study showed a marginally significant excess of homozygosity for the polymorphism located in the 3′UTR region ( P  = 0.04). No other difference in genotype and allele frequencies was found in schizophrenics as compared to the control series. The case‐control study was also carried out on estimated haplotypes, confirming a trend for association ( P  = 0.04). These results suggest that GRIN2B variations might be linked with susceptibility to schizophrenia. Replication studies on larger samples are warranted to further test this hypothesis. © 2004 Wiley‐Liss, Inc.